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Learn MoreFollicular T-helper (TFH) cells are essential for germinal center (GC) responses. TFH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here we define an antigen-independent, contact-dependent, adhesive guidance system for TFH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule that is highly expressed by GC B cells and its transmembrane binding partner semaphorin 4C (Sema4C) that is upregulated on TFH cells. Instead of effectuating repulsion as a ligand, Sema4C serves as the receptor to sense PlxnB2 and bias TFH migration inward at the GC edge to penetrate the GC territory. The absence of PlxnB2 from the GC or Sema4C from TFH cells causes TFH accumulation along the GC border, impairs TFH -B cell interactions and is associated with defective plasma cell production and affinity maturation. Therefore, Sema4C and PlxnB2 regulate GC TFH recruitment and function and optimal antibody responses. SOURCE: Hai Qi (qihai@mail.tsinghua.edu.cn) - Laboratory of Dynamic Immunobiology Tsinghua University
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